Compositions, systems, and methods for cell differentiation using targeted gene activation of DLL4 and / or VCAM1

The DNA-targeting system using DLL4 and VCAM1 gene activation with deactivated Cas proteins and guide RNAs addresses the inefficiencies of current methods, enabling cost-effective and scalable differentiation of hematopoietic progenitor cells into lymphoid progenitors for immunotherapy.

WO2026015647A1 Publication Date: 2026-01-15TUNE THERAPEUTICS INC
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Patent Information

Application Number
PCT/US2025/036991
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-06-13
Filing Date
2025-07-09
Publication Date
2026-01-15

AI Technical Summary

Technical Problem

Current methods for differentiating stem cells into lymphoid progenitor cells rely on laborious and costly external Notch-signaling ligands, making it difficult to scale and improve the production of highly functional cells for immunotherapy.

Method used

A DNA-targeting system comprising fusion proteins with DNA-binding domains that bind to target sites of DLL4 and/or VCAM1 genes, using deactivated Cas proteins and guide RNAs to enhance transcription, promoting differentiation of hematopoietic progenitor cells into lymphoid progenitors.

Benefits of technology

Facilitates efficient and scalable differentiation of hematopoietic progenitor cells into lymphoid progenitors, reducing costs and labor, and enhancing the production of functional cells for immunotherapy.

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Abstract

Provided are DNA-targeting systems, such as CRISPR-Cas / guide RNA (gRNA) systems, that bind to or target a target site in a DLL4 gene or a VCAM1 gene. In some embodiments, the provided DNA-targeting systems promote transcriptional activation of such genes to promote differentiation of hematopoietic progenitor cells into a differentiated population of cells, such as lymphoid progenitor or lymphoid cells. Also provided herein are methods and uses related to the provided compositions, for example in facilitating lymphoid progenitor cell differentiation.
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